Drug Interaction Report

MONITOR: Tetracyclines may enhance the hypoglycemic effects of insulin and insulin secretagogues (e.g., sulfonylureas, meglitinides). The exact mechanism is unknown; however, proposed mechanisms include increasing the sensitivity of insulin, increasing the half-life of insulin via inhibition of insulin degradation in the liver, interference with epinephrine-induced hyperglycemia via inhibition of glycogenolysis, and tetracycline-induced hepatotoxicity. The authors of one study suggest that tetracycline may also be able to inhibit alpha-amylase and/or alpha-glucosidase, as substrates for these enzymes have similar functional groups to those found in tetracycline. There are case reports available documenting hypoglycemia for patients on doxycycline and one case report demonstrating improved insulin sensitivity in a patient on minocycline. It is possible that other tetracyclines may possess similar abilities to lower glucose levels.

MANAGEMENT: Blood glucose should be monitored more closely during therapy with a tetracycline antibiotic. As the effects of the antibiotic may persist beyond the last dose, it is possible that patients may need to be monitored more closely until the antibiotic is fully eliminated from their body, which will differ depending on the half-life of the antibiotic involved. Insulin and insulin secretagogues may require dosage adjustments if an interaction is suspected. Patients should be apprised of the signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations), how to treat it, and to contact their doctor if it occurs unexpectedly. Conversely, patients should be observed for loss of glycemic control following completion of tetracycline therapy.

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

GENERALLY AVOID: The oral bioavailability of quinolone and tetracycline antibiotics may be reduced by concurrent administration of preparations containing polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc. Therapeutic failure may result. The proposed mechanism is chelation of quinolone and tetracycline antibiotics by di- and trivalent cations, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. Reduced gastrointestinal absorption of the cations should also be considered.

MANAGEMENT: Concomitant administration of oral quinolone and tetracycline antibiotics with preparations containing aluminum, calcium, iron, magnesium, and/or zinc salts should generally be avoided. Otherwise, the times of administration should be staggered by as much as possible to minimize the potential for interaction. Quinolones should typically be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation preparations, depending on the quinolone and formulation. Likewise, tetracyclines and polyvalent cation preparations should typically be administered 2 to 4 hours apart. The prescribing information for the antibiotic should be consulted for more specific dosing recommendations.